Unraveling Copy Number Alterations in Pediatric B-Cell Acute Lymphoblastic Leukemia: Correlation with Induction Phase Remission Using MLPA.

OBJECTIVE: Acute Lymphoblastic Leukemia (ALL) is the most common malignancy occurring in children. Copy number alterations (CNA) like PAX5, CDKN2A/2B, PAR1 Region, ETV6, IKZF1, BTG1, and RB1 gene deletion are important genetic events that define and prognosticate B-cell ALL. Thus, this study aimed to evaluate associations of CNA with induction phase remission status in childhood B-cell ALL. METHODS: This study was observational with a cross-sectional design at the Dharmais Cancer Hospital, Harapan Kita Mother and Children Hospital, and Tangerang Regional Public Hospital. We evaluated 74 pediatric B-cell ALL cases with 1-18-year-olds. Genomic DNA was analyzed by Multiplex Ligation Dependent Probe Amplification Assay (MLPA). This study used the P335 ALL-IKZF1 panel kit, which contains several ALL-related genes. The patient's clinical and laboratory characteristics were collected from medical records from January to December 2019. RESULT: We observed gene copy number alteration in children with B-Cell ALL. PAX5 was the most commonly observed gene deletion, followed by CDKN21/2B, ETV6, IKZF1, BTG1, RB1, and PAR1 Region. Based on gene mutations, only the PAX5 had a significant association with the remission status of pediatric B-cell ALL (p-value <0.05; OR = 3.91). It showed that patients with PAX5 gene mutations have 3.9 times the risk of no remission and/or relapse compared to those without PAX5 gene mutations. CONCLUSION: Patients with mutations in the PAX5 gene have a higher chance of not achieving remission and/or experiencing relapse than those without such mutations. The MLPA method can be utilized for examining copy number alterations, which is valuable for achieving more precise stratification in diagnosis.. Further research is needed to expand upon this finding.

Disease-Related Malnutrition in Pediatric Patients with Chronic Disease: A Developing Country Perspective.

Malnutrition is widely known to affect growth in children. There are many studies focusing on malnutrition globally in relation to limited food access; however, there is only limited research on disease-related malnutrition, especially in chronic conditions and particularly in developing countries. This study aims to review articles on the measurement of malnutrition in pediatric chronic disease, especially in developing countries where there are resource limitations in identifying nutritional status in pediatric chronic disease with complex conditions. This state-of-the-art narrative review was conducted through search of literatures through 2 databases, and identified 31 eligible articles published from 1990 to 2021. This study found no uniformity in malnutrition definitions and no consensus regarding screening tools for the identification of the malnutrition risk in these children. In developing countries where resources are limited, instead of focusing on finding the best tools to identify the malnutrition risk, the approach should be directed toward developing systems that work best according to capacity and allow for a combination of anthropometry assessment, clinical evaluation, and observation of feeding access and tolerance on a regular basis.

Palliative Home Visit Intervention and Emergency Admission in Pediatric Cancer Children: A Randomized Controlled Trial.

Palliative care model can be carried out at home, in the community, or in long-term home care. Home visits in palliative care have important role in providing a continuity of care and psychosocial support to both the patient and their parents/caretakers. This study is aimed to determine the impact of home visit program to the frequency of emergency room (ER) admissions in children with cancer. METHODS: Randomized controlled trial of 60 pediatric patients with malignancies who were given palliative care (a 3-months home visit) and those who were not. Patients consisted of cancer children aged 2-18 years old. Emergency room admissions from the last three months were recorded before patients were enrolled. A two-way communication between a trained health worker and patients with or without their parents were conducted as the intervention. Interventions were given in six sessions (1 session every 2 weeks). During study period, ER admissions were recorded further. Data was analyzed using bivariate analysis, OR calculations were performed. RESULTS: In the intervention group, 11 children (36.7%) had fewer ER admissions, while 4 (13.3%) had more and 15 children (50%) had constant ER admissions, respectively. Meanwhile, only 2 children (7.7%) were found to have fewer ER admissions in the control group. Others in this group have varying results, 11 children (42.3%) were found to have more admissions to the ER and 13 children (50%) had constant ER admissions. In the intervention group, ER admissions were reduced by 10 visits, while in the control group, the admissions were increased by 16 visits (OR 4.77, 95% CI 1.29-17.65; p=0.018). CONCLUSION: Palliative home visit provides care matched to patient and family needs, trained parents to be skillful in managing child, and enabling avoidance of unnecessary hospitalizations (4.7 times).

Home-based Palliative Intervention to Improve Quality of Life in Children with Cancer: A Randomized Controlled Trial.

OBJECTIVE: Over the past few years, an integrated approach of palliative care (PC) to chronic and/or life-threatening conditions care has been widely used. Home-based PC (HBPC) service is developed to meet the needs of patients at home; however, it has not been used widely. This study is aimed at determining the benefits of integrated HBPC for the quality of life (QoL) and symptoms intensity in Indonesian children with malignancies. METHOD: A randomized controlled trial was carried out to compare the quality of life between patients who were given PC (a three-month home visit) and those who did not receive PC (control group). Each group was constituted of thirty children with cancer and aged 2-18 years old and were consulted by a palliative team. The participants were randomly allocated to two groups. In the first and twelfth weeks of the intervention, all patients were assessed using the Pediatric Quality of Life Inventory (PedsQLTM) questionnaire cancer module 3.0 (report by proxy or self-report). Symptoms intensity (pain, anorexia, sleep disturbance) were scored by using Edmonton Symptoms Assessment Scale (ESAS). The mean score and each dimension score of both groups were compared and analyzed using bivariate analysis. RESULTS: In total, fifty participants were included in the study. A significant difference was found between the two groups in terms of the mean total score in control group 62.39 and intervention group 81.63 (p<0.001). The QoL was improved in the intervention group, while it was declined in the control group as the disease progressed. The main improvements were in the pain and nausea aspects (p<0.001), followed by procedural anxiety (p=0.002), treatment anxiety (p=0.002), and worry (p=0.014). Palliative intervention significantly reduced sleep disturbances (p=0.003) and anorexia (p<0.001). CONCLUSION: Home-based PC improved several aspects of QoL and caused better symptom management in children with malignancies. An early intervention concurrent with the underlying treatment can improve QoL in these children.

Correlation of Pediatric Palliative Screening Scale and Quality of Life in Pediatric Cancer Patients.

CONTEXT: Palliative care in children is used to be only intended for those in near end-of-life phase. Ideally, palliative intervention should be given since the first time of cancer diagnosis. Palliative care is introduced from the beginning of the treatment by acknowledging that it helps to ensure an ongoing focus on the quality of life (QOL) so that children still can enjoy their life. Several approaches have been used to identify children with the need of palliative care. AIMS: The aim was to describe the use of Paediatric Palliative Screening Scale (PaPaS Scale) and its depiction to the QOL of children with malignancies. SETTINGS AND DESIGN: A cross-sectional study was conducted in sixty children age 2-18 years with malignancies, who were consulted to the palliative team. SUBJECTS AND METHODS: Sixty participants were recruited randomly during the study. PaPaS Scale and QOL (using PedsQL™ cancer module 3.0) were assessed at the same time. Cutoff points of 67 for parent-proxy report and 68.9 for self-report were used, those who have scores <67 and <68.9 were grouped as low QOL group. PaPaS scale was divided into three groups: (1) no palliative care needs (score 10-14), (2) considered palliative care (15-24), and (3) need for palliative (≥25). STATISTICAL ANALYSIS: Differences between palliative score and QOL were analyzed using Chi-square and Fisher test. RESULTS: Children who have lower QOL based on parent-proxy report (<67) included 25 children; they consist of 16 children (64%) with score 10-14, four children (16%) with score 15-24, and five children (20%) with score ≥25. Children with higher QOL (16 children) consist of ten children (62.5%) with score 10-14, four children (25%) scores 15-24, and two children (12.5%) with score ≥25. In the self-report, children with low QOL (eight children) consist of four children (50%) with score 10-14, four children (50%) with score 15-24, and no children with score ≥ 25. Children with higher QOL (11 children) consist of eight children (72.2%) with score 10-14, two children (18.2%) with scores 15-24, and one child (9.1%) with score ≥25. Statistical analysis showed no correlation between PaPaS score and QOL of children with malignancies in parent-proxy report (P = 0.89) and self-report (P = 0.37). CONCLUSIONS: This study showed that children with malignancies already had lower QOL despite the low PaPaS scale they had. The results of this study support the provision of early palliative intervention, starting with a small proportion of intervention to improve the QOL of cancer child.

Prevalence of anemia and iron profile among children and adolescent with low socio-economic status.

BACKGROUND: A national health survey in Indonesia conducted in 2013 showed that the prevalence of anemia in school-aged children and adolescents tripled from a survey conducted in 2007. Children and adolescents are particularly susceptible to iron deficiency anemia (IDA) and iron deficiency (ID) because of their rapid growth and puberty. Teenage girls are at risk because of their menstrual bleeding. Low socioeconomic status in children and adolescents is also a strong risk factor for experiencing iron deficiency. Studies regarding the prevalence of ID and IDA in Indonesia still vary and are lacking. This study aims to describe the prevalence of anemia in children and adolescents with low socioeconomic conditions. METHODS: This is a cross-sectional study conducted at two schools in the suburbs of Jakarta on children and adolescents aged 6-18 years old. Personal data and laboratory identities (complete peripheral blood count, reticulocyte hemoglobin content, ferritin, transferrin saturation, and C-reactive protein) were collected to determine iron status. Analysis was performed using SPSS program version 22.0. RESULTS: The overall prevalence of anemia was 14.0%. The prevalence of IDA, ID without anemia, and iron depletion was 5.8%, 18.4%, and 4.3%, respectively. The prevalence of IDA, ID, and iron depletion was higher in females than in males. CONCLUSION: The overall prevalence of anemia in children and adolescents is lower than the national data. Special consideration needs to be taken for the female population, who are more at risk of developing ID and IDA.

Low-Dose Maintenance Intravenous Iron Therapy Can Prevent Anemia in Children with End-Stage Renal Disease Undergoing Chronic Hemodialysis.

Iron deficiency anemia is common in children with end-stage renal disease (ESRD) on long-term hemodialysis receiving erythropoiesis-stimulating agents. One approach to maintain the iron profile and hemoglobin levels is maintenance therapy with regular low doses of intravenous (IV) iron after initial iron repletion therapy; however, evidence for the benefits of this approach is lacking. This study evaluated the effect of IV iron maintenance therapy on anemia in children on regular hemodialysis. This retrospective cohort study included 41 pediatric ESRD patients with normal hemoglobin and iron status who underwent regular hemodialysis at the Pediatric Dialysis Unit of Cipto Mangunkusumo Hospital, Indonesia, between January 2015 and April 2019. Among these, 21 received IV iron maintenance therapy with two doses of 2 mg/kg of IV iron sucrose every 2 weeks (the treatment group) and 20 did not (the comparison group). Changes in hemoglobin and transferrin saturation were assessed after 6 weeks of observation and compared between the two groups. There was a significant reduction in the mean hemoglobin level compared with the baseline level in the comparison group (21 g/L; 95% CI, 9.3-33 g/L; p=0.001) but not in the treatment group (0.7 g/L; 95% CI, -6.6-8 g/L; p=0.84). The risk of anemia was lower in the treatment group (relative risk = 0.42; 95% CI, 0.22-0.79; p=0.003). Although majority of the patients had high baseline ferritin level, this study indicates that in our setting, ferritin may not be a reliable parameter to review the iron status, as it can be affected by chronic inflammation. Hence, the decision to start IV iron maintenance therapy in patients with hyperferritinemia should consider the patient's clinical condition and morbidity. To conclude, the coadministration of IV iron maintenance therapy is beneficial for maintaining hemoglobin levels and preventing anemia in children with ESRD who are undergoing regular hemodialysis, have achieved the target hemoglobin levels, and have normal iron status.

The corrected QT interval prolongation in adolescents with cardiac iron overload ß-thalassemia major.

BACKGROUND AND OBJECTIVES: Iron-induced cardiomyopathy remains the leading cause of mortality in ß-thalassemia major patients. The T2* magnetic resonance imaging (MRI) technique is the gold standard for iron load detection, yet it is expensive and not widely available especially in the developing countries. Some previous studies showed that QTc interval could be used as an early detection of cardiac iron overload. This study aimed to evaluate the diagnostic value of QTc interval as a marker of early detection of cardiac iron overload in adolescent beta thalassemia major patients. METHODS: We prospectively evaluated electrocardiography (ECG) parameter of QTc interval in 50 ß-thalassemia major patients aged 10-18 years. All participants had a 12-lead ECG evaluation, echocardiogram and cardiac MRI T2* examination within three months (average 15 days). They were categorized as cardiac iron overload (MRI T2* < 20 millisecond) and non-cardiac iron overload (MRI T2* > 20 millisecond). RESULTS: Of the 50 patients, the male to female ratio was 1.08:1 and the mean age was 13.7 ± 2.43 years. All participants showed normal systolic and diastolic function using conventional echocardiography. The mean QTc interval was significantly different between cardiac iron overload group (464.44 ± 20.35 ms) and noncardiac iron overload group (431.09 ± 32.29) (p= 0.001). Diagnostic study of QTc interval resulted in AUC 0.8 (p= 0.002). Calculated sensitivity and specificity of QTc interval were 0.88 and 0.73 respectively, with cut-off point of 449 ms. CONCLUSION: Cardiac iron overload is associated with QTc prolongation in adolescents. QTc interval of 449 ms could be considered as a cut-off point of cardiac iron overload.

The Effect of Combination of Steroid and L-Asparaginase on Hyperglycemia in Children with Acute Lymphoblastic Leukemia (ALL).

Background: Hyperglycaemia is a common side effect of steroid and L-asparaginase combinations, occurring most often during acute lymphoblastic leukemia (ALL) induction phase. To date in Indonesia, it has not been obtained data on the incidence of hyperglycemia in children with ALL in the induction phase and how the role of combinations of L-asparaginase and different type of steroid used. The purpose of this study is to determine the incidence of hyperglycemia in children ALL induction phase, knowing the difference between prednisone and dexamethasone (in combination with L-asparaginase) in causing hyperglycemia in children with ALL and determine the relationship of other factors related to hyperglycaemia. Methods: This was a prospective analytic study with a pre- and post-test design, conducted in three hospitals (Cipto Mangunkusumo Hospital, Dharmais Cancer Hospital, and Gatot Soebroto Hospital). Patient's blood glucose levels (BGL) were checked at the 3rd (pretest), 4th, 5th and 6th week of protocol (post-test). Result: Of the 57 patients, 5.2% had hyperglycemia. The patients' age ranged from 1.4 years old to 15.8 years old (6.7 years old). There was no relationship between age, central nervous system (CNS) infiltration, leukocytosis, Down syndrome, nutritional status, family history of diabetes, infections and ALL stratification with hyperglycemia (p>0.05). Dexamethasone has more chance of obtaining higher mean rate of change in BGL compared to prednisone. (p < 0.05; RR 10.68; CI 95% 1.52-74.73). Conclusion: The incidence of hyperglycemia in this study is 5.2%. Dexamethasone, in combination with L-asparaginase, despite having no difference in causing hyperglycemia, has an increased risk of changing BGL compared to prednisone.

N-terminal-pro-b-type natriuretic peptide levels and cardiac hemosiderosis in adolescent ß-thalassemia major patients.

BACKGROUND: Iron-induced cardiomyopathy remains the leading cause of mortality in patients with ß-thalassemia major. Iron overload cardiomyopathy, which may be reversible through iron chelation, is characterized by early diastolic dysfunction. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker of diastolic dysfunction. AIM: The aim of the study is to evaluate the diagnostic value of NT-proBNP as a surrogate marker of iron overload examined with magnetic resonance imaging T2-star (MRI T2*). METHODS: Sixty-eight ß-thalassemia major patients (10-18 years) with no signs of heart failure underwent NT-proBNP measurement before routine transfusion. All participants prospectively underwent cardiac MRI T2* examination within 3 months (median 19 days). Patients were divided as cardiac hemosiderosis (cardiac MRI T2* <20 ms) and nonhemosiderosis (cardiac MRI T2* >20 ms). RESULTS: Of 68 patients, the male-to-female ratio was 1:1.1 and the median age was 14.1 years (range: 10-17.8 years). NT-proBNP levels were not different between hemosiderosis and nonhemosiderosis patients (P = 0.233). Further receiver operating characteristic analysis resulted in no significant correlation of NT-proBNP and MRI T2* (area under the curve 0.393, P = 0.233). CONCLUSION: Measurement of NT-proBNP levels cannot be used for early detection of cardiac iron overload in adolescent with ß-thalassemia major.